crossing96/oncoscreening huggingface dataset:
Bladder preservation by neoadjuvant chemotherapy followed by concurrent chemoradiation for muscle-invasive bladder cancer: experience at Sindh Institute of Urology & Transplantation (SIUT).	OBJECTIVE: To identify any additional benefit and note the safety profile of neoadjuvant chemotherapy prior to concurrent chemoradiation in muscle-invasive bladder cancer. METHODS: Forty three patients with T2b-T4N0M0 bladder cancer underwent maximal TURBT followed by neoadjuvant chemotherapy cisplatinum 75 mg/m[2] D1+ gemcitabine 1000 mg/m[2] D1, D8 & D15 repeated every 28 days for three cycles followed by concurrent radiation 65Gy and weekly cisplatinum 30 mg/m[2] or gemcitabine 100 mg/m[2]. Complete response (CR) was defined as no tumour seen on cystoscopy and biopsy. The disease control and overall survival were determined by Kaplan and Meier method and statistical inferences with the log-rank test. Cox regression analysis was used to find different prognostic factors. RESULTS: Out of 43, thirty two patients (78.04%) achieved CR at time of cystoscopic evaluation. Six patients who did not achieve CR (14.63%) underwent salvage cystectomies, remaining were not operable. At the median follow up of 36 months, overall survival was 61%. Local recurrences were seen in 3 patients (10%) (2 pT1, 1pT2), distant metastases were seen in 2 patients (6.6%); 27/41 were alive, of whom 23 (56.1%) were retaining intact disease free bladders. The Tumour stage, incomplete TURBT and presence of hydronephrosis were important prognostic factors (log-rank p values 0.0001, 0.0001 and 0.001 respectively). CONCLUSION: Neoadjuvant chemotherapy followed by concurrent chemoradiation was tolerable with better bladder preservation and overall survival.	bladder
Investigation of anal sphincter function following Mainz pouch type II urinary diversion after radical cystectomy.	PURPOSES: Our aim was to evaluate the anal sphincter function following cystectomy with urinary diversion of Mainz pouch II. METHODS: Seventy-six patients were involved in our survey, and the cohort was for two groups divided. The first group was a retrospective review of 40 patients with examination of the state of continence. Comparative examinations on anal sphincter function and the quality of life survey were carried out. The second group consisting of 15 patients underwent a prospective investigation including rectal manometry in both the pre- and postoperative periods. Measurements of resting anal sphincter pressure (RASP), maximal anal closing pressure (MACP) and the function of the recto anal inhibitions reflex were taken. RESULTS: In the first part of our investigation, 80% of the patients were considered as continent. There were no significant differences observed between RASP values in the cases of continent as well as of incontinent patients (79.2 ± 2 vs. 73.6 ± 68.4 mmHg, p = 0-53); however, the MACP values of the continent patients were significantly higher (204.3 ± 22.8 vs. 117.3 ± 14 mmHg, p = 0.001). In the course of the second experiment, both the RASP (86.3 ± 18.7 vs. 76.1 ± 13.9 mmHg p = 0.0049) and the MACP (232.2 ± 53.8 vs. 194.1 ± 74.5 mmHg, p = 0.0054) were detected as decreasing in the case of the incontinent group. CONCLUSIONS: A decrease in rectal sphincter function is responsible for incontinence following Mainz pouch type II diversion, and this dysfunction can be correlated with the surgery. Ureterosigmoideostomy is therefore considered as a useful method of urinary diversion only in selected cases with proven good sphincter function.	bladder
Accelerated MVAC chemotherapy in patients with advanced bladder cancer previously treated with a platinum-gemcitabine regimen.	BACKGROUND: Gemcitabine plus cisplatinum was shown to exert comparable activity and a different toxicity profile when compared to the methotrexate, vinblastine, doxorubicin, cisplatinum (MVAC) regimen in patients with advanced bladder cancer. Accelerated MVAC (aMVAC, the four drugs being administered every 2 weeks with granulocyte colony-stimulating factor (G-CSF)) is better tolerated than conventional MVAC, with a trend for improved activity. There is no standard of care after failure of gemcitabine-platinum (GP) chemotherapy. Our aim was to assess the activity and toxicity of accelerated MVAC as second-line treatment. METHODS: We reviewed data from patients previously treated with GP who had received aMVAC at two institutions at the time of disease progression. RESULTS: Forty-five patients received aMVAC after GP: 18 (40%) and 27 (60%) had received GP in the adjuvant and the metastatic settings, respectively. The median time to progression (TTP) after first-line GP was 9.3 months. The response rate for aMVAC was 61%, including 4/38 (10%) complete responses. Median time to progression and median overall survival (OS) were 5.8 and 14.2 months, respectively. Median TTP and OS were 9.6 and 16.5 months when GP was used in the adjuvant setting and 4.4 and 5.7 months when GP was used in the metastatic setting. Grade 3-4 toxicities were observed in 31 patients (69%), including four sepsis-related deaths. CONCLUSION: aMVAC exerts clinical activity after previous treatment with GP, especially when GP was used in the adjuvant setting. aMVAC should however be administered with caution due to toxicity.	bladder
Tumor-promoting macrophages induce the expression of the macrophage-specific receptor CD163 in malignant cells.	Tumor-associated macrophages (TAMs) represent a distinct malignancy-promoting phenotype suggested to play a key role in tumor formation and metastasis. We aimed to investigate the expression of the monocyte/macrophage-restricted receptor CD163 in bladder tumor biopsies and assess the potential mechanism inducing the CD163 expression in tumor cells. A high CD163 mRNA expression (n = 87) was significantly associated with a poor 13-year overall survival (log-rank test, χ(2) = 8.931; p = 0.0028). Moreover, CD163 mRNA expression was significantly increased in muscle invasive (T2-T4), p = 0.017, and aggressive (grade III/IV) cancers (p = 0.015). The expression strongly correlated with local expression of IL-6 (r = 0.72; p <0.0001) and IL-10 (r = 0.75; p <0.0001), mediators known to induce CD163 expression in vitro. CD163 immunostaining (n = 46) confirmed the association between dense TAM infiltration and histologically advanced disease. In 39% of the biopsies, CD163 immunoreactivity was also observed in tumor cells, and CD163-expressing metastatic cells were identified in lymph node biopsies (n = 8). Bladder cancer cell lines did not express CD163; however, when cocultured with macrophages the bladder cancer cell expression of CD163 was significantly induced in an IL-6/IL-10 independent manner. In conclusion, we show a strong association between CD163 mRNA expression in bladder cancer biopsies and poor patient outcome. CD163 expression was not confined to the infiltrating TAMs, but was also expressed by a significant portion of the malignant cells in both tumors and lymph nodes. CD163 expressing tumor cells may constitute a subpopulation of tumor cells with a phenotypic shift associated with epithelial-to-mesenchymal transition (EMT) and increased metastatic activity induced by TAMs.	bladder
Paraganglioma of urinary bladder: an unusual presentation. pitfalls in diagnosis and treatment.	Paragangliomas of urinary bladder are extremely rare which usually present with characteristic clinical picture in about half of the cases. We report a case where the presentation was unusual, leading to initial misdiagnosis corrected on histological review.	bladder
Decreasing operative time and incontinence rates in patients treated with radical cystectomy and urethral diversion: a prospective randomized trial using a new suturing device (CAPIO).	PURPOSE: Radical cystectomy and orthotopic urinary diversion has been associated with significant long surgery time and postoperative urinary incontinence. We undertook a prospective randomized study to investigate the potential decrease in surgery time and improvement in the continence rate using a new suturing device compared with the traditional suture ligation, which is used for urethro-ileal anastomosis after radical cystectomy and orthotopic diversion for invasive bladder carcinoma. MATERIALS AND METHODS: Between April 2005 and March 2010, 50 consecutive patients (37 men and 13 women) were recruited for the study. They were all subjected to radical cystectomy and W ileal neobladder orthotopic diversion by two senior surgeons. They were divided and randomized into two equal groups according to the methods of urethro-ileal anastomosis. The preoperative characteristics of both groups were equally distributed. One group underwent urethro-ileal anastomosis by the CAPIO suturing device, and the other group subjected to the usual stitches by needle older. Operative and early postoperative parameters were assessed. We followed the patients for 6 months postoperatively. RESULTS: The preoperative parameters of the two groups were equally distributed with no statistically significant difference in any parameter. There were no intraoperative deaths. The mean time spent for urethro-ileal anastomosis in CAPIO group was 10.2 ± 1.4 min versus 19.6 ± 2.4 min, which was statistically significant (P value = 0.0001). Also, the mean blood loss was less in the CAPIO group (P value 0.05). As regard the early postoperative follow-up, the postoperative continence rate was significantly better in the CAPIO group than in the classic suturing group. CONCLUSIONS: CAPIO as a new suturing device significantly shortened the time needed to achieve the urethro-ileal anastomosis with better early postoperative continence rate. It makes urethral stump accessible at any time during surgery. It also enables surgeons to do anastomosis at any time after cystectomy with any number of sutures.	bladder
Selenoproteins in bladder cancer.	Selenoproteins with genetically encoded selenium (Se) are very important in response to oxidative stress, redox balance and regulation of various metabolic and developmental processes. Although increased circulating Se has been associated with 33% risk reduction of bladder cancer, there are little data on selenoprotein expression at the protein and genetic level from both human and animal studies. Data from the Mammalian Gene Collection (MGC) Project clearly showed that highest mRNA expression in human urinary epithelium for TRXR1 (thioredoxin reductase 1), GPX1 (glutathione peroxidase 1), SEP15 (15 kDa selenoprotein), SELT (selenoprotein T) and SEPW1 (selenoprotein W1). Although bladder tumor has been characterized by increased Se, GPX and TRXR activity, circulating Se and GPX was interestingly decreased in these cancer patients. As such, selenoprotein expression in urinary epithelium may be involved in bladder cancer (development, progression and recurrence) and may play a significant role in chemotherapeutic intervention. Despite these findings, the role of selenoproteins in bladder cancer has rarely been investigated and the significance of selenoproteins in normal and malignant uroepithelium remains poorly understood.	bladder
[Assessments of progression in non-muscle-invasive bladder cancer].	We retrospectively studied 463 patients with primary non-muscle-invasive bladder cancer diagnosed between 1999 and 2008 at two facilities (Kawasaki Municipal Ida Hospital and Yokohama Minami Kyosai Hospital). In this study, disease progression was defined as invasion to the muscle or further (upstage) and presence of metastasis (metastasis). We detected progression in 22 cases, including 18 upstages and 4 metastasis. Univariate analysis showed that factors associated with progression were T category (pT1 p< 0.0001), grade (high grade p< 0.0001, G3 p< 0.0001) and number of tumors (multiple p=0.0213). Multivariate analysis showed that the only equivocal factor associated with progression was T category (T1). Use of a second tansurethral resection for high-grade pT1 cases was unrelated to progression. Among the patients with progression, many had a more advanced T category at the time of radical treatment, and the results of treatment were poor. The factors associated with progression of bladder cancer should be investigated in more detail, so that early radical treatment can be initiated in eligible patients.	bladder
Cancer stem-like cells contribute to cisplatin resistance and progression in bladder cancer.	A variety of cancer stem-like cells (CSCs) have been shown to be responsible for cancer tumorigenicity, relapse and metastasis. Despite several reports demonstrating the presence of CSCs in human bladder cancer, their identities are still under debate, and few studies have examined their roles in cisplatin resistance and related tumor progression. In this study, a subpopulation of CSCs was enriched following cisplatin selection from the bladder cell line T24. The cisplatin-resistant T24 cells displayed a greater self-renewal capacity as demonstrated by higher levels of sphere formation and stem cell marker expression, contained a larger proportion of side population cells and exhibited higher tumorigenicity. They also possessed epithelial-mesenchymal transition characteristics. Furthermore, a strong correlation between the levels of Bmi1 and Nanog expression and the degree of malignancy of urothelial cell carcinomas tissues was observed. We provide the first direct evidence that CSC-like cells exist in the population of cisplatin-resistant bladder cancer cells and may play a role in the progression and drug resistance of bladder cancer.	bladder
Paclitaxel-hyaluronan hydrosoluble bioconjugate: mechanism of action in human bladder cancer cell lines.	OBJECTIVES: A previously described hydrosoluble paclitaxel-hyaluronan bioconjugate appears particularly well suited for treatment of superficial bladder cancer because of its in vitro cytotoxic profile against urothelial carcinoma (UC) cell lines and in vivo biocompatibility. The aim of this work was to assess the mechanism of action of the bioconjugate in UC cells. MATERIALS AND METHODS: Expression of CD44 and RHAMM hyaluronan-binding receptors in RT-4 and RT-112/84 UC cell lines, interaction of fluorochrome-labeled bioconjugate with tumor cells, CD44 modulation upon incubation with the compound or free hyaluronan, and caspase activation were assessed by flow cytometry. Cytotoxicity was studied by the MTT assay. Analysis of bioconjugate intracellular localization and effects on β-tubulin organization was carried out by confocal microscopy. RESULTS: The paclitaxel-hyaluronan bioconjugate bound to UC tumor cells entered intracellular compartments through a saturable and energy-dependent mechanism that involved CD44, as assessed by blocking with specific antibody. Upon internalization, the bioconjugate accumulated into lysosomes where the esteric bond between paclitaxel and the hyaluronan moiety was cleaved, leading to cytoplasmic diffusion of the free drug, caspase activation, and disruption of the β-tubulin microtubular mesh with subsequent cell death. CONCLUSIONS: Conjugation of paclitaxel to hyaluronan results in a new chemical entity, characterized by selective targeting to polymer receptors on plasma membrane and cell entry through receptor-mediated endocytosis, followed by lysosomal accumulation. Ultimately, the active molecule is released, fully preserving the cytotoxic potential and profile of clinically used free paclitaxel.	bladder
Quality of lymphadenectomy is equivalent with robotic and open cystectomy using an extended template.	PURPOSE: Extended lymph node dissection for bladder cancer provides better staging, cancerous node removal and potentially survival. Minimally invasive techniques have been criticized about the ability to adequately perform extended lymph node dissection. We compared the extended lymph node dissection quality of robotic and open cystectomy by assessing node yield and positivity. MATERIALS AND METHODS: We compared extended lymph node dissection in 120 open and 35 robotic cystectomy cases. Extended lymph node dissection included skeletonization of structures in each nodal group below the aortic bifurcation (common iliac, external iliac, obturator, hypogastric and presacral nodes). Nodes were processed identically but submitted as 1 or 2 packets for robotic cases and as 10 or more packets for open surgery cases. RESULTS: The mean±SD node count in the open group was 36.9±14.8 (range 11 to 87) and in the robotic group the mean yield was 37.5±13.2 (range 18 to 64). Only 12 of 120 open (10%) and 2 of 35 robotic (6%) cases had fewer than 20 nodes. A total of 36 open (30%) and 12 robotic (34%) cases were node positive. Open extended lymph node dissection identified 80% and 90% confidence of accurate staging as pN0 when obtaining 23 and 27 nodes, respectively. A node count of 23 or 27 was achieved in 87% and 77% of open cases, and in 91% and 83% of robotic cases, respectively. Of patients with open surgery 36% received neoadjuvant chemotherapy compared to 31% of those with robotic surgery. CONCLUSIONS: No difference was identified in the lymph node yield or the positive node rate when comparing open and robotic extended lymph node dissection. Local recurrence and survival data are needed to confirm whether the 2 techniques are oncologically equivalent.	bladder
Antitumor effects of cis-urocanic acid on experimental urothelial cell carcinoma of the bladder.	PURPOSE: We determined the effect of protodynamic therapy against bladder cancer cells in vitro and in vivo. We investigated cis-urocanic acid in rat bladder cancer cell cultures and in an orthotopic rat urothelial carcinoma model to assess its safety and antiproliferative activity. MATERIALS AND METHODS: The rat bladder cancer cell line AY-27 was exposed to cis-urocanic acid (BioCis Pharma, Turku, Finland) at pH 6.5 or 7.4 for 2 hours. Cell viability was measured by colorimetric assay at 24 and 48 hours. For in vivo experiments AY-27 cells were instilled into the acid treated bladder of 17 rats. After 4, 7 and 10 days 14 rats were treated intravesically with cis-urocanic acid 6% (weight per volume) or vehicle. Rats were sacrificed on day 12 and the bladders were dissected. Immunohistochemical staining was done to assess apoptosis (caspase-3) and cell proliferation (Ki-67) in vivo. RESULTS: Cis-urocanic acid caused dose dependent, pH dependent inhibition of AY-27 cell proliferation, showing the protodynamic action at concentrations of 0.5% and 1%. At higher cis-urocanic acid doses complete cell death was observed. All tumors detected in animals treated with vehicle were muscle invasive (stage T2 or greater) but only 43% of tumors were muscle invasive in the cis-urocanic acid treated group (p=0.049). There was no difference in the percent of apoptotic or proliferating tumor cells between treatment groups. No signs of toxicity were observed. CONCLUSIONS: Cis-urocanic acid showed direct antiproliferative activity against rat bladder cancer cells in vitro and antitumor effects in vivo. It may have therapeutic potential as an intravesical agent for nonmuscle invasive bladder cancer.	bladder
Bilateral ureteral complete obstruction with huge spontaneous urinoma formation in a patient with advanced bladder cancer.	Spontaneous rupture of the collecting system with extravasation of urine and urinoma formation is usually associated with urinary tract obstruction by a ureteral calculus. Tumor growth is an extremely rare cause of urinary extravasation. Here we report a case of bilateral obstructive uropathy with a huge spontaneous left retroperitoneal urinoma caused by advanced infiltrative transitional cell carcinoma of the urinary bladder. The point of leakage was located in the left renal pelvis. The urinary leakage ceased after percutaneous nephrostomy drainage, and the patient subsequently underwent radical cystoprostatectomy. Histopathology revealed a high-grade urothelial carcinoma of the urinary bladder with pelvic lymph node metastasis. The patient refused any adjuvant treatment and expired 6 months after the operation from disseminated metastasis from bladder cancer.	bladder
External validation of a risk model to predict recurrence-free survival after radical cystectomy in patients with pathological tumor stage T3N0 urothelial carcinoma of the bladder.	PURPOSE: Patients with stage pT3N0 urothelial bladder cancer vary in outcome after radical cystectomy. To improve prognosis estimation a model was recently developed that defines 3 risk groups for recurrence-free survival based on pT substaging, lymphovascular invasion and positive surgical margin. We present what is to our knowledge the first external validation of this risk model. MATERIALS AND METHODS: Analogous to the risk model derivation cohort our study group comprised 472 patients with stage pT3, pN0, cM0 disease without perioperative chemotherapy and with a median followup of 42 months (IQR 20-75). The primary end point was recurrence-free survival. The effect of variables was determined by univariate and multivariate Cox regression analysis, and predictive accuracy was determined by ROC analysis. RESULTS: Stage pT3aN0 and pT3bN0 cases showed significantly different recurrence-free survival after 5 years (51% vs 29%, p<0.001). In the multivariate Cox model pT3 substage (HR 1.86, p<0.001), lymphovascular invasion (HR 1.48, p=0.002), positive surgical margins (HR 1.90, p=0.030) and patient age with a dichotomy at 70 years (HR 1.51, p=0.001) had an independent effect on recurrence-free survival. In the low (221 patients or 47%), intermediate (184 or 39%) and high (67 or 14%) risk groups the 5-year recurrence-free survival rate was 55%, 45% and 13%, respectively (p<0.001). The concordance index of the risk model to predict recurrence-free survival was 0.64 (95% CI 0.59-0.69). CONCLUSIONS: This user friendly risk model can be recommended to estimate prognosis in patients with stage pT3N0 after radical cystectomy. Patients at high risk showed clearly compromised recurrence-free survival and should be included in adjuvant therapy studies.	bladder
Celastrol decreases specificity proteins (Sp) and fibroblast growth factor receptor-3 (FGFR3) in bladder cancer cells.	Celastrol (CSL) is a naturally occurring triterpenoid acid that exhibits anticancer activity, and in KU7 and 253JB-V bladder cells, CSL induced apoptosis, inhibited growth, colony formation and migration and CSL decreased bladder tumor growth in vivo. CSL also decreased expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and several Sp-regulated genes/proteins including vascular endothelial growth factor, survivin and cyclin D1 and fibroblast growth factor receptor-3, a potential drug target for bladder cancer therapy, has now been characterized as an Sp-regulated gene downregulated by CSL. The mechanism of Sp downregulation by CSL was cell context-dependent due to activation of proteosome-dependent (KU7) and -independent (253JB-V) pathways. In 253JB-V cells, CSL induced reactive oxygen species (ROS) and inhibitors of ROS blocked CSL-induced growth inhibition and repression of Sp1, Sp3 and Sp4. This response was due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of miR-27a and miR-20a/17-5p, respectively, which regulate expression of these transcriptional repressors. Thus, the anticancer activity of CSL in 253JB-V cells is due to induction of ROS and ROS-mediated induction of Sp repressors (ZBTB4/ZBTB10) through downregulation of miR-27a and miR-20a/17-5p.	bladder